Smart Intraoperative Guidance for Pediatric Brain Tumor Surgery Brain tumors is serious neurological disorders that affect more than 40,000 children worldwide each year. For the majority of children with brain tumors, complete surgical resection optimizes outcomes. Brain tumors often are similar in appearance to normal brain parenchyma, despite their distinctive pathophysiological characteristics. Accurate demarcation of brain tumors, therefore, is difficult to achieve intra-operatively, because modern diagnostic technologies like magnetic resonance imaging fail to reliably distinguish brain tumors from normal brain, and their availability in the operating room is limited due to their prohibitive cost. The ultimate goal of our research team is to improve the management of brain tumors in children. Since surgical removal of brain tumors is the most effective therapy and its success hinges upon the completeness of tumor removal, we set out to develop an intraoperative guidance system that can detect the presence of brain tumor at the resection front with high accuracy. The central hypothesis of this application is that a combined optical imaging and spectroscopy approach, when used correctly, can directly detect in vivo pathophysiological traits of pediatric brain tumors and thereby provide accurate detection of brain tumors at the resection front intraoperatively. Moreover, the envisioned optical brain tumor detection system, once developed, will be integrated into a surgical microscope for seamless and reliable operation. The accuracy of the system will be verified in an in vivo human study. The proposed work is innovative because it utilizes the non-destructive tissue characterization capability of optical spectroscopy and imaging to directly detect the in vivo pathophysiological characteristics of pediatric brain tumors. Moreover, the multimodal hybrid imaging and spectroscopy system developed in this project will investigate multiple pathophysiological features of brain tumors to enhance the accuracy of intraoperative brain tumor detection. It is expected that, by the end of this three-year project, the accuracy of the new intraoperative tumor detection system will be verified. Moreover, the underlying pathophysiological characteristics of pediatric brain tumors that enable intraoperative detection using diffuse reflectance spectroscopy and optical imaging will be determined. Completion of this research project should positively impact the management of pediatric brain tumors, because it will produce a new means by which neurosurgeons can objectively optimize the outcomes of brain tumor surgeries, thereby improving the prognoses of patients, and reducing the emotional and financial burdens endured by patients and their families.